The present project is concerned with myocardial protection during ischemic cardiac arrest with emphasis upon metabolic manipulation to improve preservation. Various adjunctive models have been combined with standard techniques of hypothermia (local cardiac cooling) and cardioplegia and include: 1) provision of surplus metabolic substrate (stored myocardial glycogen) prior to ischemic arrest, 2) provision of substrate during the period of anaerobic arrest, and 3) administration of fatty acid substrate during the aerobic recovery period. Presently, additional data are being obtained to more thoroughly evaluate a possible beneficial effect of fatty acid substrate during aerobic recovery when a hypermetabolic state exists; current studies inccude the use of an isovolumic intraventricular balloon model for evaluation of cardiac function. Coronary blood flow is measured directly. The sampling of coronary blood permits measurement of metabolic substrates and products. Tissue samples are obtained to determine concentration of the cyclic nucleotides,cyclic AMP and cyclic GMP. Cyclic nucleotide concentrations have been found to be valuable indicators of myocardial preservation and this phase of the project has assumed increasing importance.